Division of Microbiology, National Institute of Health Sciences, Tokyo, Japan.
Toxicol Lett. 2010 Feb 1;192(2):150-4. doi: 10.1016/j.toxlet.2009.10.020. Epub 2009 Oct 24.
Deoxynivalenol (DON) and nivalenol (NIV), trichothecene mycotoxins, are secondary metabolites produced by Fusarium fungi. Trichothecene mycotoxins cause immune dysfunction, thus leading to diverse responses to infection. The present study evaluated the effect of DON and NIV on nitric oxide (NO) production by RAW264 cells stimulated with lipopolysaccharide (LPS). LPS-induced NO production was reduced in the presence of these toxins. The transcriptional activation and expression of inducible NO synthase (iNOS) by LPS were also repressed by these toxins. DON or NIV inhibited LPS-induced expression of interferon-beta (IFN-beta), which plays an indispensable role in LPS-induced iNOS expression. These results indicate that DON and NIV inhibit the LPS-induced NO and IFN-beta production, which both play an important role for host protection against invading pathogens, and suggests that the inhibition of these factors may be involved in the immunotoxic effects of these mycotoxins.
脱氧雪腐镰刀菌烯醇（DON）和雪腐镰刀菌烯醇（NIV）是由镰刀菌产生的次生代谢物。单端孢霉烯族毒素会导致免疫功能障碍，从而对感染产生不同的反应。本研究评估了 DON 和 NIV 对脂多糖（LPS）刺激的 RAW264 细胞中一氧化氮（NO）产生的影响。这些毒素存在时，LPS 诱导的 NO 产生减少。LPS 诱导的诱导型一氧化氮合酶（iNOS）的转录激活和表达也被这些毒素抑制。DON 或 NIV 抑制 LPS 诱导的干扰素-β（IFN-β）表达，IFN-β 在 LPS 诱导的 iNOS 表达中起着不可或缺的作用。这些结果表明，DON 和 NIV 抑制 LPS 诱导的 NO 和 IFN-β 的产生，这两者在宿主抵御入侵病原体的保护中都起着重要作用，这表明抑制这些因子可能参与了这些霉菌毒素的免疫毒性作用。
